tbuckley/cabot-search huggingface dataset:
Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome
Authors: Christine Lebrun-Frénay, Aksel Siva, Maria Pia Sormani, Cassandre Landes-Chateau, Lydiane Mondot, Francesca Bovis, Patrick Vermersch, Caroline Papeix, Eric Thouvenot, Pierre Labauge, Françoise Durand-Dubief, Husnu Efendi, Emmanuelle Le Page, Murat Terzi, Nathalie Derache, Bertrand Bourre, Robert Hoepner, Rana Karabudak, Jérôme De Seze, Jonathan Ciron, Pierre Clavelou, Sandrine Wiertlewski, Omer Faruk Turan, Nur Yucear, Mikael Cohen, Christina Azevedo, Orhun H. Kantarci, Darin T. Okuda, Daniel Pelletier, Pierre Branger, Mouloud Abrous, Hélène Zéphir, Julie Petit, Sandra Vukusic, Céline Gelet, Clarisse Carra-Dallière, Xavier Ayrignac, Mélanie Russello, David Laplaud, Alina Gaultier, Fabienne Le Frère, Céline Callier, Cynthia Caillon, Eglantine Gueydan, Céline Louapre, Damien Galanaud, Aurelian Ungureanu, Sylvie Coudoin, Benjamin Hebant, Emmanuel Gerard, Christine Vimont, Damien Biotti, Fabrice Bonneville, Noellie Freitas, Taskin Duman, Erhan Kilic, Melih Tutuncu, Ugur Uygunoglu, Sena Destan, Sedat Sen, Christoph Friedli, Franca Wagner, Lea Weber, Annaig Tchoubar, Emilie Dumont, Asli Eryilmaz, Tanguy Roman, Christopher Pelletreau, Aurélie Grateau, Yanica Mathieu, Sarhan Yaiche, Felix Rintelen, Isabel Firmino, Aymeric De Chastenier, Amel Gheribenblidia, Burcu Zeydan
Journal: JAMA Neurology (2023)

Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system.
Fractional Flow Reserve–Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial
Authors: Frederik M. Zimmermann, Victoria Y. Ding, Nico H.J. Pijls, Zsolt Piroth, Albert H.M. van Straten, Laszlo Szekely, Giedrius Davidavicius, Gintaras Kalinauskas, Samer Mansour, Rajesh Kharbanda, Nikolaos Östlund-Papadogeorgos, Adel Aminian, Keith G. Oldroyd, Nawwar Al-Attar, Nikola Jagic, Jan-Henk E. Dambrink, Petr Kala, Oskar Angeras, Philip MacCarthy, Olaf Wendler, Filip Casselman, Nils Witt, Kreton Mavromatis, Steven E.S. Miner, Jaydeep Sarma, Thomas Engstrøm, Evald H. Christiansen, Pim A.L. Tonino, Michael J. Reardon, Hisao Otsuki, Yuhei Kobayashi, Mark A. Hlatky, Kenneth W. Mahaffey, Manisha Desai, Y. Joseph Woo, Alan C. Yeung, Bernard De Bruyne, William F. Fearon
Journal: Circulation (2023)

Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. URL: https://www. gov; Unique identifier: NCT02100722.
Unintentional Pediatric Ingestion of Cannabis—Addressing a Growing Public Health Risk
Authors: Thomas Tobin, James Xie, Kyle George
Journal: JAMA Pediatrics (2023)

This Viewpoint discusses the growing unintentional ingestion of cannabis and copycat products by children and urges clinicians, legitimate cannabis companies, large consumer brands, state attorneys general, and national legislators to provide solutions and education to adult users.
Websites Selling Direct-to-Consumer Anti-Mullerian Hormone Tests
Authors: Alexis Johnson, Rachel Thompson, Brooke Nickel, Patti Shih, Karin Hammarberg, Tessa Copp
Journal: JAMA Network Open (2023)

Importance The recent provision of direct-to-consumer (DTC) Anti-Mullerian Hormone (AMH) testing in several countries has been contentious, particularly due to concerns about judicious testing and informed consent. Objective To describe and analyze information on websites that sell DTC AMH tests. Design, Setting, and Participants Qualitative study including content analysis of text information from websites in multiple countries that sell AMH tests DTC. The top 50 search results from 4 different internet search strings were captured and reviewed for eligibility. Data were extracted in March 2022 and analyzed from April 2022 to July 2023. Main outcomes and measures Themes and categories were derived from the website content using a conventional inductive approach, with a particular focus on information content, quality and accuracy, as well as the tone and language used. Results Twenty-seven websites across 7 different countries formed the sample for analysis. Information varied considerably across websites and was organized into 6 overarching categories: (1) whether a test description was included (25 websites [93%]); (2) statements about what the test can do, which included indicating ovarian reserve (26 websites [96%]) and indicating likelihood of conceiving (20 websites [74%]); (3) statements about the usefulness of the test result, which included enabling women to adjust their reproductive timeline (11 websites [41%]) and determining whether egg freezing was a viable option (8 websites [30%]); (4) blood collection method (ie, through a laboratory or an at-home sample); (5) promotion tactics, such as stating the convenience of testing (24 websites [89%]) and using language promoting empowerment and control (7 websites [26%]); and (6) statements about limitations of the test, which included polycystic ovary syndrome falsely inflating AMH levels (13 websites [48%]) and that it cannot accurately predict chances of conceiving (9 websites [33%]). Conclusion and relevance In this qualitative study including content analysis, most websites selling DTC AMH tests included false and misleading claims which might lead consumers to purchase an AMH test in the belief that it can reliably predict fertility potential and age of menopause. Depending on the test result, this may in turn lead to misplaced anxiety or reassurance about one’s fertility and modifications to subsequent conception or contraceptive plans and behavior.
Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering
Authors: Alex G. Hamilton, Kelsey L. Swingle, Ryann A. Joseph, David Mai, Ningqiang Gong, Margaret M. Billingsley, Mohamad‐Gabriel Alameh, Drew Weissman, Neil C. Sheppard, Carl H. June, Michael J. Mitchell
Journal: Advanced Healthcare Materials (2023)

The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T cell activity in the tumor microenvironment. While clinical approaches to inhibiting the PD-1 pathway using antibody blockade have been broadly successful, these approaches lead to widespread PD-1 suppression, increasing the risk of autoimmune reactions. This study reports the development of an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient gene knockdown in T cells. In developing this platform, interesting interactions are observed between the two RNA cargoes when co-encapsulated, leading to improved expression and knockdown characteristics compared to delivering either cargo alone. This messenger RNA (mRNA)/small interfering RNA (siRNA) co-delivery platform is adopted to deliver chimeric antigen receptor (CAR) mRNA and siRNA targeting PD-1 to primary human T cells ex vivo and strong CAR expression and PD-1 knockdown are observed without apparent changes to overall T cell activation state. This delivery platform shows great promise for transient immune gene modulation for a number of immunoengineering applications, including the development of improved cancer immunotherapies.
Reexamining Quality Assessment and Effect Size Reporting Among Studies Showing Major Changes in Depressive Symptoms—Reply
Authors: Ross D. Neville, Sheri Madigan
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Bypassing Closest Stroke Center for Intracerebral Hemorrhage—Not So Fast!
Authors: Paul M. Wechsler, Babak B. Navi
Journal: JAMA Neurology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
The Tumor Immune Microenvironment Architecture Correlates with Risk of Recurrence in Head and Neck Squamous Cell Carcinoma
Authors: Donald T. Weed, Serena Zilio, Christie McGee, Boutheina Marnissi, Zoukaa Sargi, Elizabeth Franzmann, Giovana Thomas, Jason Leibowitz, Elizabeth Nicolli, David Arnold, Silvio Bicciato, Paolo Serafini
Journal: Cancer Research (2023)

Abstract Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC. Significance: Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.
Incidence, Stage, Treatment, and Survival of Noncardia Gastric Cancer
Authors: Merel J. M. van Velzen, Michelle Braemer, Grard A. P. Nieuwenhuijzen, Johanna W. van Sandick, Peter D. Siersema, Jelle P. Ruurda, Marcel Verheij, Manon C. W. Spaander, Laurens V. Beerepoot, Nadia Haj Mohammad, Hanneke W. M. van Laarhoven, Rob H. A. Verhoeven
Journal: JAMA Network Open (2023)

Gastric cancer is the fifth most common cancer worldwide, and investigating its incidence, characteristics, treatment, and outcomes over the past decades can help in selecting clinical strategies and future research directions.To analyze the trends in incidence, staging, and treatment of gastric cancer.This nationwide, population-based cohort study included patients diagnosed with noncardia gastric cancer (NCGC) between 1989 and 2021 in the Netherlands.Differences in tumor characteristics, treatment, and survival were analyzed per fixed time periods (1989-1993, 1994-1998, 1999-2003, 2004-2008, 2009-2013, 2014-2018, and 2019-2021).In total, 47 014 patients (median [IQR] age, 73 [64-80] years; 28 032 [60%] male patients) were identified with mostly adenocarcinomas of the antrum region (when location was known). Age-standardized incidence decreased from 20.3 to 6.1 per 100 000 person-years between 1989 and 2021. During the study period, unknown T and N stages were recorded less frequently, and metastatic disease was diagnosed more frequently (1989-1993: 2633 of 9493 patients [28%]; 2019-2021: 1503 of 3200 patients [47%] in 2019-2021). Over time, fewer patients with metastatic disease underwent surgery with or without other treatment modalities (68% in 1989-1993 vs 64% in 2019-2021), and palliative chemotherapy in metastatic NCGC increased from 9% to 40%. For patients with nonmetastatic disease, 5-year relative survival improved from 28% (95% CI, 26.5%-29.2%) to 36% (95% CI, 33.5%-37.6%) between 1989 and 2021. For patients with nonmetastatic disease undergoing a resection, 5-year survival increased from 40% (95% CI, 38.3%-41.8%) to 51% (95% CI, 47.9%-53.3%). For patients with metastatic disease, 1-year relative survival increased from 10% (95% CI, 8.7%-11.1%) to 19% (95% CI, 17.2%-21.6%), but 3-year relative survival remained poor at 5% (95% CI, 3.6%-7.5%).In this nationwide cohort study involving 47 014 patients diagnosed with NCGC (1989-2021), the results showed a decrease in incidence, more accurate staging, a shift in treatment modalities, and improved patient survival.
Fasting-Mimicking Diet Drives Antitumor Immunity against Colorectal Cancer by Reducing IgA-Producing Cells
Authors: Ziwen Zhong, Hao Zhang, Ke Nan, Jing Zhong, Qichao Wu, Lihong Lu, Ying Yue, Zhenyu Zhang, Miaomiao Guo, Zhiqiang Wang, Jie Xia, Yun Xing, Ying Fu, Baichao Yu, Wenchang Zhou, Xingfeng Sun, Yang Shen, Wankun Chen, Jie Zhang, Jin Zhang, Duan Ma, Yiwei Chu, Ronghua Liu, Changhong Miao
Journal: Cancer Research (2023)

As a safe, feasible, and inexpensive dietary intervention, fasting-mimicking diet (FMD) exhibits excellent antitumor efficacy by regulating metabolism and boosting antitumor immunity. A better understanding of the specific mechanisms underlying the immunoregulatory functions of FMD could help improve and expand the clinical application of FMD-mediated immunotherapeutic strategies. In this study, we aimed to elucidate the role of metabolic reprogramming induced by FMD in activation of antitumor immunity against colorectal cancer. Single-cell RNA sequencing analysis of intratumoral immune cells revealed that tumor-infiltrating IgA+ B cells were significantly reduced by FMD treatment, leading to the activation of antitumor immunity and tumor regression in murine colorectal cancer models. Mechanistically, FMD delayed tumor growth by repressing B-cell class switching to IgA. Therefore, FMD-induced reduction of IgA+ B cells overcame the suppression of CD8+ T cells. The immunoregulatory and antitumor effects of FMD intervention were reversed by IgA+ B-cell transfer. Moreover, FMD boosted fatty acid oxidation (FAO) to trigger RUNX3 acetylation, thus inactivating Cα gene transcription and IgA class switching. IgA+ B-cell expansion was also impeded in patients placed on FMD, while B-cell expression of carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme of FAO, was increased. Furthermore, CPT1A expression was negatively correlated with both IgA+ B cells and IgA secretion within colorectal cancer. Together, these results highlight that FMD holds great promise for treating colorectal cancer. Furthermore, the degree of IgA+ B cell infiltration and FAO-associated metabolic status are potential biomarkers for evaluating FMD efficacy.Metabolic reprogramming of B cells induced by fasting-mimicking diet suppresses IgA class switching and production to activate antitumor immunity and inhibit tumor growth. See related commentary by Bush and Perry, p. 3493.
Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation
Authors: Jue Wang, Abigail McVicar, Yilin Chen, Hong-Wen Deng, Zhihe Zhao, Wei Chen, Yi-Ping Li
Journal: International Journal of Oral Science (2023)

Abstract The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice ( Atp6i −/− ) arrested tooth root formation, indicated by truncated Hertwig’s epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation . Atp6i −/− mice had largely decreased expression of odontoblast differentiation marker gene expression profiles ( Col1a1, Nfic, Dspp, and Osx ) in the alveolar bone. Atp6i −/− mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i −/− odontoblasts. Through treating pulp precursor cells with Atp6i −/− or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression ( Nfic, Dspp, Osx , and Runx2) . This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i −/− OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i −/− mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.
<i>Faecalibacterium prausnitzii</i> Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade
Authors: Yaqi Gao, Pingping Xu, Danfeng Sun, Yi Jiang, Xiao-Lin Lin, Ting Han, Jun Yu, Chunquan Sheng, Haoyan Chen, Jie Hong, Yingxuan Chen, Xiu-Ying Xiao, Jing-Yuan Fang
Journal: Cancer Research (2023)

Abstract Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy; however, their application is limited by the occurrence of immune-related adverse events. The gut microbiota plays important roles in the response to and toxicity of immunotherapy and Faecalibacterium prausnitzii (F. prausnitzii) has been shown to possess immunomodulatory potential. Here, we found that patients receiving ICIs who developed colitis had a lower abundance of F. prausnitzii. In vivo, immunocompetent mice administered with dextran sodium sulfate and immunodeficient NSG mice with human peripheral blood mononuclear cell transfer were treated with ICIs to study ICI-induced colitis. Dual CTLA4 and PD-1 blockade exacerbated autoimmune colitis, activated an inflammatory response, and promoted myeloid cell infiltration, with higher percentages of macrophages, dendritic cells, monocytes, and neutrophils. F. prausnitzii administration mitigated the exacerbated colitis induced by ICIs. Concomitantly, F. prausnitzii enhanced the antitumor immunity elicited by ICIs in tumor-bearing mice while abrogating colitis. In addition, administration of F. prausnitzii increased gut microbial alpha diversity and modulated the microbial composition, increasing a subset of gut probiotics and decreasing potential gut pathogens. F. prausnitzii abundance was reduced in mice that developed ICI-associated colitis. Together, this study shows that F. prausnitzii administration ameliorates ICI-induced colitis, reshapes the gut microbial composition, and enhances the antitumor activity of immunotherapy. Significance: F. prausnitzii alleviates colitis while enhancing the tumor-suppressive effects of immune checkpoint blockade, indicating that supplementation with F. prausnitzii could be a treatment strategy to mitigate immunotherapy toxicity in patients with cancer.